Maldevelopment of the kidney and urinary tract accounts for approximately 30% of renal failure in children. Acute renal failure (ARF) is the most frequent kidney-related diagnosis in adult hospitalized patients. The process of regeneration of damaged portions of the nephron following acute renal injury recapitulates the developmental process. A delineation and understanding of the molecular basis of renal organogenesis and regeneration of the nephron following ARF is a prerequisite for developing strategies for treatment and prevention. The rationale for the George M. O'Brien Center at Washington University is to continue funding for a multi disciplinary effort to delineate the molecular basis of renal organogenesis and its abnormalities and regeneration following ARF. The objectives of the Center are: a) to attract new scientific expertise into the study of developmental nephrology and ARF; b) to conduct research that integrates the disciplines of adult and pediatric nephrology, endocrinology, pathology, genetics, cellular and molecular biology and physiology; and c) to extend these basic investigations into areas that will provide the basis for an understanding of the causes for and prevention of specific developmental kidney abnormalities and the treatment of ARF. Pathophysiological processes that will be investigated include maldevelopment of the kidney and ARF, disorders of branching morphogenesis during kidney development and repair, disorders of the glomerular basement membrane and disorders of fluid and electrolyte transport resulting from aberrant maturation of the H+ATPase and Na+-K+-ATPase. The strategy for achieving these objectives is to integrate the efforts of an accomplished group of cellular and molecular-oriented biomedical scientists with interdigitating areas of expertise in the setting of an Institution with formidable resources and a strong research tradition.